J Clin Invest. 2019 Feb 1;129(2):506-508. doi: 10.1172/JCI126116. Epub 2019 Jan 14.
Neoantigen-targeted therapies have typically been based upon personalized neoantigen-specific vaccines; however, in this issue of JCI, van der Lee et al. describe the development of a potential cellular immunotherapy targeting a "public" neoantigen derived from nucleophosmin 1 (NPM1), which is mutated in approximately 30% of acute myeloid leukemias (AMLs). The authors use reverse immunology to predict, and biochemically confirm, NPM1-derived neoepitopes (ΔNPM1) and then generate high-avidity T cell clones and retrovirally transduced T cell populations that kill NPM1-mutated AML. This study provides a general approach to adoptive cellular therapy that can be applied to targeting other tumors with public neoantigens.
新兴抗原靶向治疗通常基于个性化的新兴抗原特异性疫苗；然而，在本期 JCI 中，van der Lee 等人描述了一种针对核磷蛋白 1（NPM1）衍生的“公共”新兴抗原的潜在细胞免疫疗法的发展，该抗原在大约 30%的急性髓系白血病（AML）中发生突变。作者使用反向免疫学来预测和生化验证 NPM1 衍生的新表位（ΔNPM1），然后生成高亲和力 T 细胞克隆和逆转录病毒转导的 T 细胞群体，这些细胞能够杀伤 NPM1 突变的 AML。这项研究提供了一种通用的过继细胞治疗方法，可以应用于靶向其他具有公共新兴抗原的肿瘤。
